84 articles - From Friday Aug 12 2022 to Friday Aug 19 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Ann Oncol |
ESMO Expert Consensus Statements on Cancer Survivorship: promoting high-quality survivorship care and research in Europe. ESMO can actively contribute in the efforts of the oncology community towards a) promoting the development of high-quality survivorship care programs, b) providing educational material and c) aiding groundbreaking research by reflecting on priorities and by supporting research networking. |
meta-analyses and systematic reviews
| CA Cancer J Clin |
Clinician communication strategies associated with increased uptake of the human papillomavirus (HPV) vaccine: A systematic review. Determinations about a causal relationship were limited by the small numbers of randomized controlled trials. There is also opportunity for more research to determine the effects of motivational interviewing and cancer-prevention messaging. |
RCT, clinical trials, retrospective studies, etc…
| Ann Oncol |
Association of Tumor-infiltrating Lymphocytes (TILs) with Survival Depends on Primary Tumor Sidedness in Stage III Colon Cancers (NCCTG N0147) [Alliance]. The association of TIL densities with patient survival differed by primary tumor sidedness and clinical risk group, suggesting that TILs should be interpreted in this context among stage III colon cancers. |
Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response. Durvalumab added to NACT in TNBC significantly improved survival despite a modest pCR increase and no adjuvant component of durvalumab. Additional studies are needed to clarify the optimal duration and sequence of CPIs in the treatment of early TNBC. |
Safety and efficacy of pralsetinib in RET fusion-positive non-small cell lung cancer including as first-line therapy: update from the ARROW trial. Pralsetinib treatment produced robust efficacy and was generally well tolerated in treatment-naïve patients with advanced RET fusion-positive NSCLC. Results from the confirmatory phase III AcceleRET Lung study (NCT04222972) of pralsetinib versus standard of care in the first-line setting are pending. |
| Blood |
Aberrant MYCN expression drives oncogenic hijacking of EZH2 as a transcriptional activator in peripheral T cell lymphoma. Remarkably, EZH2 was found to be an essential co-factor for the transcriptional activation of the MYCN-driven gene expression program, which was independent of methyltransferase activity, but dependent on phosphorylation by CDK1. MYCN-driven T cell lymphoma was sensitive to EZH2 degradation or CDK1 inhibition, which displayed synergy with FDA-approved HDAC inhibitors. |
Discovery of novel predisposing coding and noncoding variants in familial Hodgkin lymphoma. While KDR and KLHDC8B have previously been reported, PAX5, GATA3,IRF7, EEF2KMT, and POLR1E represent novel observations. Although there may be environmental factors influencing lymphomagenesis, we observed segregation of candidate germline variants likely to predispose HL in most of the pedigrees studied. |
Germline predisposition variants occur in myelodysplastic syndrome patients of all ages. If presumed germline variants were included, the yield of P/LP variants would increase to 11% and by adding suspicious variants of unknown significance, it would rise further to 12%. The high frequency of P/LP germline variants in our study supports comprehensive germline genetic testing for al MDS patients regardless of their age at diagnosis. |
Preservation of fecal microbiome is associated with reduced severity of Graft-versus-Host Disease. Importantly, Clostridial and butyrate-producer abundance, as well as S/F anaerobe ratio were predictors of longer overall survival; higher abundance of butyrate producers, and higher S/F anaerobe ratio were associated with decreased risk of GVHD-related death. These findings suggest that the intestinal microbiome can serve as a biomarker for outcomes of allo-HCT patients with GVHD. |
Prognostic impact of NPM1 and FLT3 mutations in patients with AML in first remission treated with oral azacitidine. Median OS with Oral-AZA vs placebo was 28.2 vs 16.2 months, respectively, for FLT3mut/MRD- patients, and 24.0 vs 8.0 months for FLT3mut/MRD+ patients. In multivariate analyses, Oral-AZA significantly improved survival independent of NPM1 or FLT3 mutational status, cytogenetic risk, or post-IC MRD status. |
Progression and Survival of Monoclonal B-cell Lymphocytosis (MBL): A screening study of 10,139 individuals. In this large screening cohort, we observed similar survival among individuals with and without LC-MBL, yet individuals with LC-MBL have a 4-fold increased risk of lymphoid malignancies. Accumulating evidence indicates that there are clinical consequences to LC-MBL, a condition that affects 8-10 million adults in the United States. |
The use of pluripotent stem cells to generate diagnostic tools for transfusion medicine. The RBCs derived from these iPSCs (iRBCs) are compatible with standard laboratory assays used worldwide and can determine the precise specificity of Rh antibodies in patient plasma. Rh-engineered iRBCs can provide a readily accessible diagnostic tool and guide future efforts to produce an alternative source of rare RBCs for alloimmunized patients. |
VWF-targeted thrombolysis to overcome rh-tPA resistance in experimental thrombotic stroke models. However, Microlyse, but not rh-tPA, reduced cerebral lesion volumes (13.9±11.4mm3; p<0.001; 23.6±11.1mm3; p=0.188; 30.3±10.9mm3, respectively vs vehicle). These findings support broad applicability of Microlyse in ischemic stroke irrespective of the thrombus composition. |
| Blood Adv |
A gene expression assay based on chronic lymphocytic leukemia activation in the microenvironment to predict progression. In multivariate analysis, the CLL15 score (HR: 1.83, 95%CI 1.32-2.56; p<0.001) and the IPS-E CLL (HR: 2.23, 95%CI 1.59-3.12; p<0.001) were independently associated with TtFT. The newly developed and validated CLL15 assay successfully translates previous gene signatures, such as the microenvironment signaling, into a new gene expression-based assay with prognostic implications in CLL. |
Characterizing the role of the immune microenvironment in multiple myeloma progression at a single cell level. These alterations were further accompanied by an enrichment of non-clonal memory B cells and an increase of CD14 and CD16 monocytes in MM compared to its precursor stages. These results provide crucial information of the immune changes associated with the progression to clinical MM and can help to develop immune based strategies for patient stratification and early therapeutic intervention. |
Dynamic EASIX Scores Closely Predict Nonrelapse Mortality After Allogeneic Hematopoietic Cell Transplantation. EASIX scores are dynamic and variably concordant with NRM when analyzed longitudinally, and patterns differ between HCT platforms. Compared to pre-HCT evaluation, post-HCT EASIX scores may better predict risk of NRM as patients acquire additional endothelial injury and toxicities. |
Elucidating Parasite and Host Cell Factors Enabling Babesia Infection in Sickle Red Cells under Hypoxic/Hyperoxic Conditions. Multiple factors, including oxygenation and its impact on cell-shape, HbF positivity, redox status, and parasite pleiotropy allow Babesia propagation in sickle RBCs. Our studies provide a cellular and molecular basis of natural resistance to Babesia which will aid in defining novel therapies against human babesiosis. |
Late effects in mantle cell lymphoma patients treated with or without autologous stem cell transplantation. The majority of patients died from their lymphoma and not from another cause or treatment complication. Taken together, our results imply that the vast majority of the post-treatment healthcare needs are related to the lymphoma disease itself, thus, indicating the need for more efficient treatment options. |
Lymphatic coagulation and neutrophil extracellular traps in lung-draining lymph nodes of COVID-19 decedents. This study introduces lymphatic coagulation in lungs and LDLNs as a clinical manifestation of severe COVID-19 and suggests the involvement of NETosis of lymphatic-trafficking neutrophils. It further suggests that lymphatic clotting may correlate with impaired formation or maintenance of germinal centers necessary for robust antiviral antibody responses, although further studies are needed to determine whether and how lymphatic coagulation impacts adaptive immune responses. |
Mutations of TFPI-binding exosites on factor VII cause bleeding phenotypes in factor VII deficiency. Additionally, the thrombin generation assay revealed a significant prolongation of lag time in al FVII variants. Our study explains how mutations of TFPI-binding exosites of FVII can lead to bleeding phenotypes in individuals carrying these aberrancies. |
Pembrolizumab for the treatment of disease relapse following allogeneic hematopoietic stem cell transplantation. An acquired EZH2 mutation was identified at relapse in a DLBCL patient who achieved an initial complete response to pembrolizumab, which was associated with downregulated HLA expression on malignant B cells, implicating EZH2 mutations as a potential immune escape mechanism following PD-1 blockade therapy. In conclusion, post-alloHCT pembrolizumab is feasible and associated with objective responses in relapsed lymphoid malignancies, but can induce severe irAEs, requiring vigilant monitoring. |
Safety and Efficacy of Classical Complement Pathway Inhibition with Sutimlimab in Chronic Immune Thrombocytopenia. These results demonstrate that in some ITP patients autoantibodies activate the classical complement pathway, accelerating platelet destruction or impairing platelet production, contributing to treatment failure. C1s inhibition may be a safe and beneficial therapeutic approach for patients with chronic/refractory ITP. |
sCD25 as an independent adverse prognostic factor in adult HLH patients: results of a multicenter retrospective study. In multivariate analysis sCD25 remained the only significant prognostic factor (p = 0.005). Our results suggest that sCD25 could be a useful marker for the prognosis of patients with HLH that might help to stratify therapeutic interventions. |
Targeted therapy with the mutant IDH2 inhibitor enasidenib for high-risk IDH2-mutant myelodysplastic syndrome. Enasidenib is an effective treatment option for mIDH2 MDS, both in combination with azacitidine for treatment naïve high-risk MDS, and as a single agent after prior HMA therapy. This trial is registered at as NCT03383575. |
| Blood Cancer J |
Importantly, LY41157 rapidly cleared sBCMA from circulation of MM-bearing NSG mice reconstituted with human T cells and significantly enhanced anti-MM efficacy of PL33 with prolonged host survival. Taken together, these results further support ongoing combination BCMA-targeting immunotherapies with GSI clinical studies to improve patient outcome. |
Phenotypically-defined stages of leukemia arrest predict main driver mutations subgroups, and outcome in acute myeloid leukemia. NPM1 mutations correlate with most mature stages of leukemia arrest together with TET2 or IDH mutations in granulocyte progenitors-like AML or with DNMT3A mutations in monocyte progenitors-like AML. Overall, we demonstrate that AML is arrested at specific stages of myeloid differentiation (SLA classification) that significantly correlate with AML genetic lesions, clinical presentation, stem cell properties, chemosensitivity, response to therapy, and outcome. |
| Haematologica |
In vivo stabilization of a less toxic asparaginase variant leads to a durable anti-tumor response in acute leukemia. Our results show a comparable long lasting durable anti-leukemic effect between the standard-of-care PEG-asparaginase and ABD-ErA-TM L-asparaginase, but with fewer co-glutaminase related acute side effects. Since the toxic side effects of current L-asparaginases often result in treatment discontinuation in ALL patients, this novel ErA-TM variant with ultra-low L-glutaminase co-activity and long in vivo persistence may have great clinical potential. |
Bence Jones Island in Shepherd Bay, Ninavut: a little known tribute to the legendary physician and chemist's "thé de voyage". Rae's report of his voyage in 1855, cited herein, mentioned the island and showed its position on a map of the region. We have located it on a current map of the waterways and landmasses of Nunavut using Google Earth Pro by showing its position at the approximate coordinates of latitude and longitude cited by Rae. |
Molecular monitoring of T-cell kinetics and migration in severe neurotoxicity after real-world CD19-specific chimeric antigen receptor-T cell therapy. Interestingly, a major fraction of eventually dominating hyperexpanded T-cell clones were of non-CAR-T cell derivation. These findings hint to a role of therapy-refractory T-cell clones in severe ICANS development and prompt future systematic research to determine if CAR-T cells may serve as 'door openers' and to further characterize both CARpositive and non-CAR-T cells to interrogate the transcriptional signature of these possibly pathologic T cells. |
Osteoprogenitor SFRP1 prevents exhaustion of hematopoietic stem cells via PP2A-PR72/130-mediated regulation of p300. Our findings show that osteoprogenitor Sfrp1 is essential for maintaining HSC function. Furthermore, pharmacological downregulation of nuclear Catenin beta-1/phospho-p300 association is a new strategy to restore poor HSC function. |
Potent preclinical activity of FLT3-directed chimeric antigen receptor T cell immunotherapy against FLT3-mutant acute myeloid leukemia and KMT2A-rearranged acute lymphoblastic leukemia. We further demonstrate significant in vitro and in vivo activity of bispecific CD19xFLT3CART against KMT2A-rearranged ALL and posit that this additional approach might also diminish potential antigen escape in these high-risk leukemias. Our preclinical data credential FLT3CART as a highly effective immunotherapeutic strategy for both FLT3-mutant AML and KMT2A-R ALL that is poised for further investigation and clinical translation. |
Selective inhibition of MCL1 overcomes venetoclax-resistance in a murine model of myelodysplastic syndromes. While VEN response positively correlated with MDS with excess blasts, al MDS subtypes responded to MCL1 inhibition. Treatment with combined VEN+MCL1 inhibtion was synergistic in al MDS subtypes without significant injury to normal hematopoiesis and reduced MDS engraftment in MISTRG6 mice, supporting the pursuit of clinical trials with combined BCL2+MCL1 inhibition in MDS. |
| J Hematol Oncol |
Triple MAPK inhibition salvaged a relapsed post-BCMA CAR-T cell therapy multiple myeloma patient with a BRAF V600E subclonal mutation. Here, we show the applicability, effectiveness, and tolerability the triple MAPK inhibition strategy in the context of post-BCMA CAR-T failure in specific subset of patients. The triple therapy could bridge our hospice bound RRMM patient with BRAF (V600E) to further therapeutic options where sCR was achieved. We will further evaluate triple MAPK inhibition in patients with BRAF V600E in a precision medicine clinical trial launching soon. |
| Leukemia |
Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults. Compared to negative cases, chromothripsis positive T-ALL had a significantly higher level of MYCN expression, and a significant downregulation of RGCC, which is typically induced by TP53 in response to DNA damage. Furthermore we identified mutations and/or deletions of DNA repair/genome stability genes in al cases, and an association with NUP214 rearrangements in 33% of cases. |
Comparison of scoring systems evaluating suitability for intensive chemotherapy in adults with acute myeloid leukemia-a Grand Ouest Against Leukemia (GOAL) study. Together, our findings indicate that the accuracy of currently available approaches to identify patients at increased risk of early mortality and shortened survival after intensive AML therapy is relatively limited. Caution regarding the use of available scoring systems should be warranted in clinical decision-making. |
Modified risk-stratified sequential treatment (subcutaneous rituximab with or without chemotherapy) in B-cell Post-transplant lymphoproliferative disorder (PTLD) after Solid organ transplantation (SOT): the prospective multicentre phase II PTLD-2 trial. Results with R-CHOP-21 in high-risk patients confirmed previous results. Immunochemotherapy intensification in very-high-risk patients was disappointing. |
Molecular determinants of outcomes in relapsed or refractory mantle cell lymphoma treated with ibrutinib or temsirolimus in the MCL3001 (RAY) trial. Restricted to patients with deletions/alterations in TP53, ibrutinib appeared to abrogate the deleterious impact on outcome. These data illustrate the potential to perform a molecular analysis of predictive biomarkers on routine patient samples that can meaningfully inform clinical practice. |
Single-cell ATAC-seq maps the comprehensive and dynamic chromatin accessibility landscape of CAR-T cell dysfunction. Finally, knockdown of BATF or IRF4 enhanced the killing ability, inhibited exhaustion, and prolonged the persistence of CAR-T cells in vivo. Together, our study unraveled the epigenetic regulatory mechanisms of CAR-T exhaustion and provided new insights into CAR-T engineering to achieve better clinical treatment benefits. |
| Thromb Haemost |
Circulating endothelial cells are associated with thromboembolic events in patients with antiphospholipid antibodies. This study demonstrated that endothelial injury assessed by the levels of CECs was associated with thromboembolic events in patients with aPL and/or autoimmune diseases. |
Disseminated Intravascular Coagulation score predicts mortality in patients with liver disease and low fibrinogen level. The ISTH DIC-2001 and DIC-2018 scores predicted 30-day mortality in patients with liver disease and low fibrinogen levels. The DIC score deserves further investigation in this population as it likely reflects different dimensions of the underlying disease. |
The Influence of Plasma Prekallikrein Oligonucleotide Antisense Therapy on Coagulation and Fibrinolysis Assays: a Post-hoc Analysis. Reduction of plasma prekallikrein by donidalorsen in HAE patients neither affected thrombin formation nor fibrinolytic activity. Our data suggest that partial plasma prekallikrein reduction does not influence thrombotic risk. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Ann Oncol |
Targeting the complexity of ERBB2 biology in gastroesophageal carcinoma. Multiple lines of evidence suggest that immune mechanisms involving antibody-dependent cell-mediated cytotoxicity are preponderant over intracellular signaling in anti-ERBB2 therapy action. A better comprehension of these mechanisms could leverage immune action of anti-ERBB2 therapy and elucidate efficacy of combinations associating immunotherapy and anti-ERBB2 therapy, as suggested by the recent intermediate positive results of KEYNOTE-811 trial. |
| Blood |
| CA Cancer J Clin |
The contemporary management of peritoneal metastasis: A journey from the cold past of treatment futility to a warm present and a bright future. The authors also explore the emerging role of adding hyperthermic intraperitoneal chemotherapy to the well established paradigm of CRS and systemic therapy for advanced ovarian cancer, as well as the recent clinical trials identifying the efficacy of poly(adenosine diphosphate ribose) polymerase maintenance therapy. Finally, recent data are included that explore the role of precision medicine technology in PM management that, in the future, may help further improve patient selection, identify the best systemic therapy regimens, detect actionable mutations, and identify new targets for drug development. |
| J Hematol Oncol |
Immune checkpoint modulators in cancer immunotherapy: recent advances and emerging concepts. Although the current ICI therapy is far from satisfying, a series of novel immune checkpoint molecules with remarkable preclinical and clinical benefits are being widely investigated, like the V-domain Ig suppressor of T cell activation (VISTA), which can also be called PD-1 homolog (PD-1H), and ectonucleotidases: CD39, CD73, and CD38, which belong to the ribosyl cyclase family, etc. In this review, we systematically summarized and discussed these molecules' biological structures, molecular features, and the corresponding targeted drugs, aiming to help the in-depth understanding of immune checkpoint molecules and promote the clinical practice of ICI therapy. |
Targeting macrophages in hematological malignancies: recent advances and future directions. Furthermore, reprogramming of pro-tumor macrophages to anti-tumor macrophages, and CAR macrophages (CAR-M) demonstrate anti-tumor activities. In this review, we elucidated distinct types of macrophage-targeted strategies in hematological malignancies, from preclinical experiments to clinical trials, and outlined potential therapeutic approaches being developed. |
Letters to the editors and authors’ replies
| Am J Hematol |
| Ann Oncol |
| J Hematol Oncol |
Evidence of SARS-CoV-2 spike protein on retrieved thrombi from COVID-19 patients. In addition, in al three COVID-19 thrombi analyzed for molecular biology, no SARS-CoV-2 RNA could be detected by real-time polymerase chain reaction. These data could support the hypothesis that free SP, besides the whole virus, may be the trigger of platelet activation and clot formation in COVID-19. |
Genome-wide profiling of 5-hydroxymethylcytosines in circulating cell-free DNA reveals population-specific pathways in the development of multiple myeloma. Of the top 500 gene bodies with differential 5hmC levels between MM and SMM/MGUS, the majority (94.8%) were distinct between EA and AA and enriched with population-specific pathways, including amino acid metabolism in AA and mainly cancer-related signaling pathways in EA. These findings improved our understanding of the epigenetic contribution to racial disparities in MM and suggest epigenetic pathways that could be exploited as novel preventive strategies in high-risk populations. |
Genotype-phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry. Kato partially functional variants were present in 10 out of 53 (19%) families without childhood cancer except adrenocortical carcinoma (ACC) versus 0 out of 41 families with childhood cancer other than ACC alone (P value |
Matched related transplantation versus immunosuppressive therapy plus eltrombopag for first-line treatment of severe aplastic anemia: a multicenter, prospective study. Multivariate analysis showed that first-line MRD-HSCT treatment was associated favorably with normal blood results at 6-month and FFS (P |
| Leukemia |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Blood Cancer J |
| Haematologica |
| Leukemia |